CATL1_CANLF
ID CATL1_CANLF Reviewed; 333 AA.
AC Q9GL24;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Procathepsin L;
DE EC=3.4.22.15;
DE AltName: Full=Cathepsin L1;
DE Contains:
DE RecName: Full=Cathepsin L;
DE Contains:
DE RecName: Full=Cathepsin L heavy chain;
DE Contains:
DE RecName: Full=Cathepsin L light chain;
DE Flags: Precursor;
GN Name=CTSL; Synonyms=CTSL1;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Eto Y., Hirata M., Takeuchi A., Yamamoto Y., Taga A., Taura Y.,
RA Takahashi S.Y.;
RT "RACE cloning and expression of canine cathepsin L.";
RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Thiol protease important for the overall degradation of
CC proteins in lysosomes (By similarity). Plays a critical for normal
CC cellular functions such as general protein turnover, antigen processing
CC and bone remodeling. Involved in the solubilization of cross-linked
CC TG/thyroglobulin and in the subsequent release of thyroid hormone
CC thyroxine (T4) by limited proteolysis of TG/thyroglobulin in the
CC thyroid follicle lumen (By similarity). In neuroendocrine chromaffin
CC cells secretory vesicles, catalyzes the prohormone proenkephalin
CC processing to the active enkephalin peptide neurotransmitter (By
CC similarity). In thymus, regulates CD4(+) T cell positive selection by
CC generating the major histocompatibility complex class II (MHCII) bound
CC peptide ligands presented by cortical thymic epithelial cells. Also
CC mediates invariant chain processing in cortical thymic epithelial
CC cells. Major elastin-degrading enzyme at neutral pH. Accumulates as a
CC mature and active enzyme in the extracellular space of antigen
CC presenting cells (APCs) to regulate degradation of the extracellular
CC matrix in the course of inflammation (By similarity). Secreted form
CC generates endostatin from COL18A1 (By similarity). Critical for cardiac
CC morphology and function. Plays an important role in hair follicle
CC morphogenesis and cycling, as well as epidermal differentiation (By
CC similarity). Required for maximal stimulation of steroidogenesis by
CC TIMP1 (By similarity). {ECO:0000250|UniProtKB:P06797,
CC ECO:0000250|UniProtKB:P07154, ECO:0000250|UniProtKB:P07711,
CC ECO:0000250|UniProtKB:P25975}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Specificity close to that of papain. As compared to cathepsin
CC B, cathepsin L exhibits higher activity toward protein substrates,
CC but has little activity on Z-Arg-Arg-NHMec, and no peptidyl-
CC dipeptidase activity.; EC=3.4.22.15;
CC Evidence={ECO:0000250|UniProtKB:P07711};
CC -!- ACTIVITY REGULATION: Inhibited by the propeptide produced by
CC autocleavage (By similarity). Long isoform of CD74/Ii chain stabilizes
CC the conformation of mature CTSL by binding to its active site and
CC serving as a chaperone to help maintain a pool of mature enzyme in
CC endocytic compartments and extracellular space of APCs. IFNG enhances
CC the conversion into the CTSL mature and active form (By similarity).
CC Inhibited by CST6. Inhibited by the glycopeptide antibiotic
CC teicoplanin. Inhibited by amantadine (By similarity).
CC {ECO:0000250|UniProtKB:P06797, ECO:0000250|UniProtKB:P07711}.
CC -!- SUBUNIT: Dimer of a heavy and a light chain linked by disulfide bonds.
CC Interacts with Long isoform of CD74/Ii chain; the interaction
CC stabilizes the conformation of mature CTSL.
CC {ECO:0000250|UniProtKB:P06797}.
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:P06797}. Apical
CC cell membrane {ECO:0000250|UniProtKB:P06797}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:P06797}; Extracellular side
CC {ECO:0000250|UniProtKB:P06797}. Cytoplasmic vesicle, secretory vesicle,
CC chromaffin granule {ECO:0000250|UniProtKB:P25975}. Secreted,
CC extracellular space {ECO:0000250|UniProtKB:P06797}. Secreted
CC {ECO:0000250|UniProtKB:P06797}. Note=Localizes to the apical membrane
CC of thyroid epithelial cells. Released at extracellular space by
CC activated dendritic cells and macrophages.
CC {ECO:0000250|UniProtKB:P06797}.
CC -!- PTM: During export along the endocytic pathway, pro-CTSL undergoes
CC several proteolytic cleavages to generate the CTSL single-chain and
CC two-chain mature forms, composed of a heavy chain linked to a light
CC chain by disulfide bonds (By similarity). Autocleavage; produces the
CC single-chain CTSL after cleavage of the propeptide. The cleavage can be
CC intermolecular (By similarity). {ECO:0000250|UniProtKB:P06797,
CC ECO:0000250|UniProtKB:P07711}.
CC -!- SIMILARITY: Belongs to the peptidase C1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU10088, ECO:0000255|PROSITE-ProRule:PRU10089,
CC ECO:0000255|PROSITE-ProRule:PRU10090}.
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DR EMBL; AJ279008; CAC08809.1; -; mRNA.
DR RefSeq; XP_005615836.1; XM_005615779.1.
DR RefSeq; XP_005615837.1; XM_005615780.1.
DR RefSeq; XP_005615838.1; XM_005615781.1.
DR AlphaFoldDB; Q9GL24; -.
DR SMR; Q9GL24; -.
DR STRING; 9612.ENSCAFP00000001630; -.
DR MEROPS; C01.032; -.
DR PaxDb; Q9GL24; -.
DR PRIDE; Q9GL24; -.
DR Ensembl; ENSCAFT00030008770; ENSCAFP00030007712; ENSCAFG00030004769.
DR Ensembl; ENSCAFT00030025598; ENSCAFP00030022351; ENSCAFG00030013828.
DR Ensembl; ENSCAFT00040006653; ENSCAFP00040005759; ENSCAFG00040003499.
DR Ensembl; ENSCAFT00040033001; ENSCAFP00040028714; ENSCAFG00040017888.
DR Ensembl; ENSCAFT00845005177; ENSCAFP00845004111; ENSCAFG00845002925.
DR Ensembl; ENSCAFT00845053897; ENSCAFP00845042356; ENSCAFG00845030379.
DR GeneID; 102156614; -.
DR KEGG; cfa:102156614; -.
DR CTD; 1515; -.
DR VEuPathDB; HostDB:ENSCAFG00845002925; -.
DR VEuPathDB; HostDB:ENSCAFG00845030379; -.
DR eggNOG; KOG1543; Eukaryota.
DR GeneTree; ENSGT00940000154367; -.
DR HOGENOM; CLU_012184_1_2_1; -.
DR InParanoid; Q9GL24; -.
DR OMA; CSHPQGN; -.
DR OrthoDB; 1275401at2759; -.
DR TreeFam; TF313739; -.
DR Reactome; R-CFA-1474228; Degradation of the extracellular matrix.
DR Reactome; R-CFA-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-CFA-1679131; Trafficking and processing of endosomal TLR.
DR Reactome; R-CFA-2132295; MHC class II antigen presentation.
DR Reactome; R-CFA-8939242; RUNX1 regulates transcription of genes involved in differentiation of keratinocytes.
DR Proteomes; UP000002254; Chromosome 1.
DR Proteomes; UP000002254; Chromosome X.
DR Bgee; ENSCAFG00000001149; Expressed in thymus and 47 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042583; C:chromaffin granule; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0048002; P:antigen processing and presentation of peptide antigen; ISS:UniProtKB.
DR GO; GO:0043373; P:CD4-positive, alpha-beta T cell lineage commitment; ISS:UniProtKB.
DR GO; GO:0030574; P:collagen catabolic process; ISS:UniProtKB.
DR GO; GO:0060309; P:elastin catabolic process; ISS:UniProtKB.
DR GO; GO:0034230; P:enkephalin processing; ISS:UniProtKB.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:0016540; P:protein autoprocessing; ISS:UniProtKB.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IBA:GO_Central.
DR GO; GO:0031638; P:zymogen activation; ISS:UniProtKB.
DR CDD; cd02248; Peptidase_C1A; 1.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR025661; Pept_asp_AS.
DR InterPro; IPR000169; Pept_cys_AS.
DR InterPro; IPR025660; Pept_his_AS.
DR InterPro; IPR000668; Peptidase_C1A_C.
DR InterPro; IPR039417; Peptidase_C1A_papain-like.
DR InterPro; IPR013201; Prot_inhib_I29.
DR Pfam; PF08246; Inhibitor_I29; 1.
DR Pfam; PF00112; Peptidase_C1; 1.
DR PRINTS; PR00705; PAPAIN.
DR SMART; SM00848; Inhibitor_I29; 1.
DR SMART; SM00645; Pept_C1; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00640; THIOL_PROTEASE_ASN; 1.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
DR PROSITE; PS00639; THIOL_PROTEASE_HIS; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Cytoplasmic vesicle; Disulfide bond; Glycoprotein;
KW Hydrolase; Lysosome; Membrane; Protease; Reference proteome; Secreted;
KW Signal; Thiol protease; Zymogen.
FT SIGNAL 1..17
FT /evidence="ECO:0000250|UniProtKB:P07154"
FT PROPEP 18..117
FT /note="Activation peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000026240"
FT CHAIN 118..333
FT /note="Cathepsin L"
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT /id="PRO_0000450785"
FT CHAIN 118..289
FT /note="Cathepsin L heavy chain"
FT /id="PRO_0000026241"
FT PROPEP 290..291
FT /evidence="ECO:0000250"
FT /id="PRO_0000026242"
FT CHAIN 292..333
FT /note="Cathepsin L light chain"
FT /id="PRO_0000026243"
FT ACT_SITE 138
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT ACT_SITE 277
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT ACT_SITE 300
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT SITE 106..107
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT SITE 107..108
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT SITE 112..113
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT SITE 113..114
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT CARBOHYD 222
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 135..178
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT DISULFID 169..212
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT DISULFID 270..322
FT /note="Interchain (between heavy and light chains)"
FT /evidence="ECO:0000250|UniProtKB:P07711"
SQ SEQUENCE 333 AA; 37383 MW; 033096E72B791D1F CRC64;
MNPSLFLTAL CLGIASAAPK FDQSLNAQWY QWKATHRRLY GMNEEGWRRA VWEKNMKMIE
LHNREYSQGK HGFTMAMNAF GDMTNEEFRQ VMNGFQNQKH KKGKMFQEPL FAEIPKSVDW
REKGYVTPVK NQGQCGSCWA FSATGALEGQ MFRKTGKLVS LSEQNLVDCS RAQGNEGCNG
GLMDNAFRYV KDNGGLDSEE SYPYLGRDTE TCNYKPECSA ANDTGFVDLP QREKALMKAV
ATLGPISVAI DAGHQSFQFY KSGIYFDPDC SSKDLDHGVL VVGYGFEGTD SNNKFWIVKN
SWGPEWGWNG YVKMAKDQNN HCGIATAASY PTV
